1. We have systematically analyzed the Alzheimer's brain using biochemical and histol6gical technique. Dr.Hatanpaa demonstrated that drebrin expression was downregulated more specifically than other synaptic functional proteins. He also showed that drebrin expression decreased in parallel with normal human aging. Drs.Shirao and Sekino analyzed distribution of drebrin containing synapses in the rat brain during development. Wistar rats of various developmental stages from postnatal day 0 to day 20 were transcardially perfused with 3.7% formalin and the brain was removed, postfixed, and their cryostat section was immunostained with ABC method or with immunofluorescence. Before postnatal by 10 drebrin remain to be observed in cell body, axons and dendrites. In contrast at postnatal day 14 drebrin was localized in the dendritic spines, and was not observed in cell soma.2. Then we examined whether this developmental change in drebrin distribution was observed in primary cultured neurons or not. At 7 days in culture, drebrin was observed in neurites, and its staining pattern is continuous, In the cell soma drebrin was concentrated in cortical cytoplasm. Although at this developmental stage spine formation was started, drebrin clusters were not yet observed. At 14 days in culture drebrin staining pattern was most discontinuous and patchy although thin neurites was continuously immunostained. At 21 days in culture all drebrin-staining pattern was patchy. Double immunostaining with synaptophysin and drebrin antibodies demonstrated that drebrin is accumulated in the dendritic spines. Taken together it was demonstrated that drebrin accumulation was occurred in parallel with the maturation of synaptic function, and was indicated that this accumulation was regulated by neuronal activity.